Network pharmacology combined with molecular docking and experimental verification to elucidate the effect of flavan-3-ols and aromatic resin on anxiety.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Catechin*/*analogs & derivatives; Molecular Docking Simulation* ; Flavonoids*/chemistry ; Flavonoids*/pharmacology ; Anti-Anxiety Agents*/pharmacology ; Anti-Anxiety Agents*/chemistry ; Anxiety*/drug therapy ; Catechin*/pharmacology ; Catechin*/chemistry; Animals ; Molecular Dynamics Simulation ; Male ; Network Pharmacology ; Monoamine Oxidase/metabolism ; Monoamine Oxidase/chemistry ; Behavior, Animal/drug effects ; Catechol O-Methyltransferase/metabolism ; Catechol O-Methyltransferase/chemistry ; Mice ; Protein Binding

This study investigated the potential anxiolytic properties of flavan-3-ols and aromatic resins through a combined computational and experimental approach. Network pharmacology techniques were utilized to identify potential anxiolytic targets and compounds by analyzing protein-protein interactions and KEGG pathway data. Molecular docking and simulation studies were conducted to evaluate the binding interactions and stability of the identified targets. Behavioral tests, including the elevated plus maze test, open field test, light-dark test, actophotometer, and holeboard test, were used to assess anxiolytic activity. The compound-target network analysis revealed complex interactions involving 306 nodes and 526 edges, with significant interactions observed and an average node degree of 1.94. KEGG pathway analysis highlighted pathways such as neuroactive ligand-receptor interactions, dopaminergic synapses, and serotonergic synapses as being involved in anxiety modulation. Docking studies on EGCG (Epigallocatechin gallate) showed binding energies of -9.5 kcal/mol for MAOA, -9.2 kcal/mol for SLC6A4, and -7.4 kcal/mol for COMT. Molecular dynamic simulations indicated minimal fluctuations, suggesting the formation of stable complexes between small molecules and proteins. Behavioral tests demonstrated a significant reduction in anxiety-like behavior, as evidenced by an increased number of entries into and time spent in the open arm of the elevated plus maze test, light-dark test, open field center activity, hole board head dips, and actophotometer beam interruptions (p < 0.05 or p < 0.01). This research provides a comprehensive understanding of the multi-component, multi-target, and multi-pathway intervention mechanisms of flavan-3-ols and aromatic resins in anxiety treatment. Integrated network and behavioral analyses collectively support the anxiolytic potential of these compounds and offer valuable insights for future research in this area.
(© 2024. The Author(s).)

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0 (Flavonoids)
0 (Anti-Anxiety Agents)
8R1V1STN48 (Catechin)
35HDD3NRIE (flavan-3-ol)
EC 1.4.3.4 (Monoamine Oxidase)
BQM438CTEL (epigallocatechin gallate)
EC 2.1.1.6 (Catechol O-Methyltransferase)

Date Created: 20240429 Date Completed: 20240429 Latest Revision: 20240502

20240502

PMC11058257

10.1038/s41598-024-58877-z

38684743